Much progress has been made in one's understanding of the mechanism of rickettsial actin-based motility, although the process of cell-to-cell spread remains poorly understood. This chapter examines historical and recent developments in our understanding of how rickettsiae establish intracellular infection. The focus is on the three major stages that include: (i) escape from the phagosome, (ii) intracellular growth, and (iii) actinbased motility. Several bacterial activities that may function in membrane disruption have since been discovered, including phospholipase A2 (PLA2), phospholipase D (PLD), and hemolysins (TlyA and TlyC). Each of these activities and its potential role in phagosome escape is discussed in the chapter. Interestingly, the growth kinetics for the spotted fever group rickettsiae (SFGR) species R. rickettsii did not follow the simple kinetics observed for the typhus group rickettsiae (TGR) species R.prowazekii. The function of intracellular movement is to promote cell-to-cell spread, a process that is discussed in the chapter.

Rickettsial invasion occurs in five stages over the first 20 min of infection. These include (i) adhesion to the host cell plasma membrane, (ii) engulfment, (iii) inclusion in a phagosome, (iv) phagosome lysis, and (v) release into the cytosol. (Artwork adapted from Teysseire et al. [1995] by Taro Ohkawa.)

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FIGURE 1

Rickettsial invasion occurs in five stages over the first 20 min of infection. These include (i) adhesion to the host cell plasma membrane, (ii) engulfment, (iii) inclusion in a phagosome, (iv) phagosome lysis, and (v) release into the cytosol. (Artwork adapted from Teysseire et al. [1995] by Taro Ohkawa.)

SFGR and TGR have different effects on host cell structure and physiology. (Top left) SFGR species have little effect on host cell ultrastructure at times shortly after infection (24 h). (Bottom left) However, progressive changes occur during longer infections (48 h and beyond), including dilation of the RER and outer nuclear envelope, loss of a distinct Golgi apparatus, and swollen mitochondria. Cells eventually lyse during very long infections (more than 120 h; not shown). (Top right) TGR species are initially observed in small numbers in the cytosol early in infection (30 h), and as infection progresses the number of bacteria increase with no effect on host cell ultrastructure (up to 96 h). (Bottom right) At very late times (96 to 120 h postinfection), host cell lysis and bacterial release occur. (Artwork adapted from Silverman and Wisseman [1979] and Silverman et al. [1980] by Taro Ohkawa.)

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FIGURE 2

SFGR and TGR have different effects on host cell structure and physiology. (Top left) SFGR species have little effect on host cell ultrastructure at times shortly after infection (24 h). (Bottom left) However, progressive changes occur during longer infections (48 h and beyond), including dilation of the RER and outer nuclear envelope, loss of a distinct Golgi apparatus, and swollen mitochondria. Cells eventually lyse during very long infections (more than 120 h; not shown). (Top right) TGR species are initially observed in small numbers in the cytosol early in infection (30 h), and as infection progresses the number of bacteria increase with no effect on host cell ultrastructure (up to 96 h). (Bottom right) At very late times (96 to 120 h postinfection), host cell lysis and bacterial release occur. (Artwork adapted from Silverman and Wisseman [1979] and Silverman et al. [1980] by Taro Ohkawa.)

The life cycle of SFGR observed from invasion through cell-to-cell spread. From right to left, the stages include adhesion and engulfment, inclusion in a phagosome, phagosome lysis, release into the cytosol, bacterial growth, actin-based motility, movement into a protrusion, engulfment by a neighboring cell, inclusion in a double-membrane vacuole, vacuole lysis, and release into the cytosol of the second cell. (Artwork by Taro Ohkawa.)

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FIGURE 4

The life cycle of SFGR observed from invasion through cell-to-cell spread. From right to left, the stages include adhesion and engulfment, inclusion in a phagosome, phagosome lysis, release into the cytosol, bacterial growth, actin-based motility, movement into a protrusion, engulfment by a neighboring cell, inclusion in a double-membrane vacuole, vacuole lysis, and release into the cytosol of the second cell. (Artwork by Taro Ohkawa.)

12. Clarke, D. H.,, and J. P.Fox. 1948. The phenomenon of in vitro hemolysis produced by the rickettsiae of typhus fever, with a note on the mechanism of rickettsial toxicity in mice. J. Exp. Med.88:25–41.PubMedCrossRef